NEW YORK – The Japanese Ministry of Health, Labor, and Welfare has approved the MET Inhibitor tepotinib (Merck KGaA's Tepmetko) for non-small cell lung cancer patients with MET exon 15 skipping alterations, after the drug demonstrated meaningful benefit in objective response across different lines of treatment.

Simultaneously, the agency approved ArcherDX's ArcherMET test as a companion diagnostic to identify patients eligible for treatment. The assay is designed to detect METex14 skipping alterations in both tissue and liquid biopsy samples.

Administered as a once-daily oral dose, tepotinib is the first approved MET inhibitor in Japan, designed to inhibit the oncogenic MET receptor signaling caused by MET gene alterations, including both METex14 skipping alterations and MET amplifications, or MET protein overexpression. The ArcherDx assay is the first and only assay to be approved as a CDx for the drug.

ArcherDx and Merck KGaA entered a strategic partnership in 2018 to develop CDx featuring both liquid and tissue biopsy capabilities, including the MET target now approved alongside tepotinib.

"Identifying oncogenic drivers in order to guide the course of treatment for lung cancer patients is a clinical best practice; however, there previously was no approved therapy that specifically targeted MET alterations in metastatic NSCLC," Hiroshi Sakai, director of the Division of Thoracic Oncology at the Saitama Cancer Center in Saitama, Japan, said in a statement.  "With the approval of Tepmetko, we now have a new treatment option that addresses this need, offering clinical benefit and duration of response with convenient once-daily oral dosing, representing real progress for patients with this aggressive type of lung cancer."

The Japanese approval of tepotinib is supported by data from studies of 99 patients (including 15 Japanese patients) with NSCLC with METex14 skipping alterations enrolled in the ongoing single-arm Phase II VISION study. Objective response rate as assessed by an independent review committee (the primary endpoint) was 42.4 percent in patients identified by liquid biopsy or tissue biopsy.

Median duration of response based on independent assessment was 12.4 months for both liquid biopsy- and tissue-tested patients. In a safety analysis of 130 patients, the drug was well tolerated, with the most frequent treatment-related adverse events of any grade being peripheral edema, nausea, and diarrhea. Adverse events led to permanent discontinuation in 11 patients.

"With Tepmetko, we are pleased to offer the first approved MET inhibitor in Japan, and a new option that can change the course of treatment for non-small cell lung cancer harboring METex14 skipping alterations," Belén Garijo, CEO of Healthcare and Member of the Executive Board of Merck KGaA, said in a statement. "With a focus on identifying these alterations in NSCLC patients with flexibility and precision, the companion diagnostic to Tepmetko offers both liquid and tissue biopsy testing capabilities to best support the delivery of this targeted therapy to the patients who may benefit."

Merck said it also has plans to bring the new therapy through regulatory approval in the US. The US Food and Drug Administration granted breakthrough therapy designation for tepotinib in September 2019 for patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy. EMD Serono, the biopharma arm of Merck KGaA, said it plans to file an application for review this year.

Tepotinib is also being investigated in the INSIGHT 2 study in combination with the tyrosine kinase inhibitor osimertinib in epidermal growth factor receptor (EGFR)-mutated, MET amplified, locally advanced or metastatic NSCLC that has acquired resistance to prior EGFR TKI.